{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:10:38Z","timestamp":1789693838254,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG066509"],"award-info":[{"award-number":["P30AG066509"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG062421"],"award-info":[{"award-number":["P30AG062421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K99AG082864"],"award-info":[{"award-number":["K99AG082864"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01\u2010DK121240\u201001"],"award-info":[{"award-number":["R01\u2010DK121240\u201001"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARFD\u201021\u2010851373"],"award-info":[{"award-number":["AARFD\u201021\u2010851373"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Cognition is reduced at low and high glucose, reflecting cognitive vulnerability to glucose (CVG) fluctuations. The impact of glucose fluctuations on the aging brain remains unclear. We examined whether CVG is associated with plasma biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants included\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0114 adults with type 1 diabetes assessed for processing speed and sustained attention using ecological momentary assessment (EMA) combined with continuous glucose monitoring (CGM). We characterized associations between CVG and amyloid beta (A\u03b2) 42\/40, phosphorylated tau (p\u2010tau) 181 and 217, neurofilament light chain, and glial fibrillary acidic protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>CVG was associated with all plasma biomarkers, except A\u03b2 42\/40. CVG for sustained attention exhibited strong associations with p\u2010tau biomarkers that persisted across covariate specifications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>CVG may be a useful digital phenotype of AD. It remains unclear whether CVG contributes to versus arises from neurodegeneration. We consider possible mechanisms linking cognitive vulnerability and long\u2010term glucose variability to the development of neuropathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Cognitive vulnerability to glucose (CVG) may be a useful digital phenotype of neurodegeneration.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We used cognitive ecological momentary assessment and continuous glucose monitoring to investigate CVG's associations with plasma biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Associations of CVG for sustained attention and phosphorylated tau 181 remained significant across covariates.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We discuss possible mechanisms relating glucose variability, cognition, and neurodegeneration.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70001","type":"journal-article","created":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:11:29Z","timestamp":1740874289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cognitive vulnerability to glucose fluctuations: A digital phenotype of neurodegeneration"],"prefix":"10.1002","volume":"21","author":[{"given":"Luciana Mascarenhas","family":"Fonseca","sequence":"first","affiliation":[{"name":"Elson S. Floyd College of Medicine Washington State University  Spokane Washington USA"},{"name":"Department and Institute of Psychiatry Programa Terceira Idade (PROTER, Old Age Research Group) University of S\u00e3o Paulo School of Medicine  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb W.","family":"Hawks","sequence":"additional","affiliation":[{"name":"Institute for Technology in Psychiatry McLean Hospital  Belmont Massachusetts USA"},{"name":"Department of Psychiatry Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal Schnaider","family":"Beeri","sequence":"additional","affiliation":[{"name":"Herbert and Jacqueline Krieger Klein Alzheimer's Research Center Rutgers University  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanee","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Technology in Psychiatry McLean Hospital  Belmont Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogish","family":"Kudva","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetes and Nutrition Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafaq","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetes and Nutrition Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Bulger","sequence":"additional","affiliation":[{"name":"Department of Medicine SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Grinspoon","sequence":"additional","affiliation":[{"name":"Institute for Technology in Psychiatry McLean Hospital  Belmont Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamille","family":"Janess","sequence":"additional","affiliation":[{"name":"Jaeb Center for Health Research  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Sliwinski","sequence":"additional","affiliation":[{"name":"Department of Human Development and Family Studies Pennsylvania State University, University Park  Pennsylvania USA"},{"name":"Center for Health Aging Pennsylvania State University, University Park  Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Pratley","sequence":"additional","affiliation":[{"name":"Translational Research Institute AdventHealth  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Rickels","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth S.","family":"Weinstock","sequence":"additional","affiliation":[{"name":"Department of Medicine SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmeer P.","family":"Chhatwal","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Kivis\u00e4kk","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Thi","family":"Germine","sequence":"additional","affiliation":[{"name":"Institute for Technology in Psychiatry McLean Hospital  Belmont Massachusetts USA"},{"name":"Department of Psychiatry Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi S.","family":"Chaytor","sequence":"additional","affiliation":[{"name":"Elson S. Floyd College of Medicine Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v14.i2.92"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.35"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.12.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/61.4.987S"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2021.102089"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.10.1745"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000517352"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(98)00120-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.1.71"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0212"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.09.011"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibneur.2022.12.006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1657"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00086-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-2438"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.16182"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2018.04.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14966"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3515-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.2196\/44502"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.25"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-024-01036-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13777"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13829"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.2196\/39750"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2196\/45028"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0956797615594896"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0956797614567339"},{"key":"e_1_2_9_30_1","unstructured":"R Core Team.R: A Language and Environment for Statistical Computing.R Foundation for Statistical Computing;2023."},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"issue":"4","key":"e_1_2_9_32_1","article-title":"ATN blood biomarkers are related to digital cognitive assessment in type 1 diabetes","volume":"16","author":"Fonseca LM","year":"2024","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.4485"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3758\/s13423-021-01908-x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2017.03.010"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc24-0229"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01822-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1037\/pag0000288"},{"key":"e_1_2_9_39_1","article-title":"Diabetes mellitus in the young and the old: Effects on cognitive functioning across the life span","author":"Duinkerken E","year":"2019","journal-title":"Neurobiol Dis"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab927"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019030218"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0199"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2023.0320"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S410363"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad042"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.122.264279"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12841"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12283"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-05907-6"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15205"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00133.2018"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14973"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/151979"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101619"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00939-9"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:38:19Z","timestamp":1789558699000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/alz.70001"],"URL":"https:\/\/doi.org\/10.1002\/alz.70001","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70001"}}